Differential phenotype and behavior in culture of CD34 positive cells from peripheral blood and adipose tissue.

The localization and quantification of endothelial progenitor cells (EPCs) are controversial. Circulating CD34 + cells in blood have been identified as EPCs and as biomarkers of cardiovascular disease. We discuss in this paper the current data describing differential phenotype and behavior in vitro of CD34 positive cells from the circulation and adipose tissue (AT). We also describe in brief our own findings from CD34 + cells isolated from leukopheresis cones derived from healthy platelet donors and from patients undergoing bariatric surgery. We conclude that CD34 + cells in blood and in AT are different in antigenic profile and behavior in culture. The findings described assert that CD34 + cells detected in blood previously identified as biomarkers of cardiovascular disease are predominantly HPCs rather than EPCs, and that true CD34 + EPCs can be readily identified and extracted from AT, supportive of the current evidence which suggests EPCs are resident in the tissue vasculature.

Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients.

BACKGROUND: In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation. OBJECTIVES: The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection. METHODS: Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained. RESULTS: A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction. CONCLUSIONS: A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Timing of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor initiation and allograft vasculopathy progression and outcomes in heart transplant recipients.

AIMS: Early studies from the 1990s have shown that statins improve survival and attenuate cardiac allograft vasculopathy (CAV). However, little contemporary data are available on the incremental benefit of statins with the current use of new-generation immunosuppressive agents and the use of coronary intravascular ultrasound for assessment of CAV. We sought to investigate the effect of early statin (ES) as compared with late statin (LS) initiation after heart transplantation (HT) on long-term CAV progression and clinical outcomes in a large contemporary HT cohort. METHODS AND RESULTS: We analysed a cohort of 409 adult HT recipients. CAV progression was assessed by serial coronary intravascular ultrasound volumetric measurements of the differences between baseline and last follow-up plaque volume (PV) and plaque index (PV/vessel volume ratio). CAV progression and clinical outcomes were compared between the ES (<2 years after HT) and the LS (>2 years after HT) groups. During a median follow-up of 8.2 years, ES resulted in significantly lower change (Δ) of plaque index (+3.8% ± 1.7% vs. +8.2% ± 3.6%; P = 0.0008) and PV (+0.8 ± 0.3 vs. +1.9 ± 1.2; P = 0.045) compared with LS group. In a Cox proportional hazards regression model and after adjustment for baseline characteristics, ES was associated with a 52% decreased risk of CAV-associated events (hazard ratio 0.48, 95% confidence interval: 0.27-0.91; P = 0.025) and a 42% decreased risk of the composite endpoint of all-cause mortality and CAV-associated events (hazard ratio 0.58, 95% confidence interval: 0.38-0.91; P = 0.019). CONCLUSIONS: Early initiation of statin therapy after HT results in attenuated CAV progression as well as in decreased CAV-related events and mortality.

Periprocedural Management of 172 Gastrointestinal Endoscopies in Patients with Left Ventricular Assist Devices.

The number of patients with left ventricular assist devices (LVADs) continues to increase, and gastrointestinal (GI) endoscopy is commonly required in this patient population. We retrospectively reviewed the experience of a single tertiary care center in managing patients with LVADs undergoing GI endoscopy between 2006 and 2013. After hospital dismissal from the LVAD placement, 53 patients underwent 172 GI endoscopic procedures. Gastrointestinal bleeding was the indication for endoscopy in 73.8% of patients. Median age at endoscopy was 66 years, and median time from LVAD implantation to initial endoscopy was 271 days (range, 31-1681 days). Anticoagulation or antiplatelet therapy was present within 1 week before 120 of 172 endoscopies (70%) and was withheld or actively reversed in 91 of 120 cases (76%). For sedation/anesthesia during endoscopy, 63 involved care by an anesthesiology team and 109 were performed with nursing sedation protocols. Noninvasive blood pressure techniques (conventional automated cuffs or Doppler pulses) were used for hemodynamic monitoring in 84%, arterial lines in 10%, and no blood pressure recordings documented/charted as inaccurate in 6%. Six patients died within 30 days of endoscopy with one death because of aspiration of blood and multiorgan failure. Patients with LVADs may safely undergo GI endoscopy with various individualized anesthetic/sedation models. Complications after endoscopy likely represent the acuity of this patient population.

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading.

The perioperative management of patients with left ventricular assist devices undergoing noncardiac surgery.

OBJECTIVE: To describe the perioperative management of patients with left ventricular assist devices (LVADs) who require general anesthesia while undergoing noncardiac surgery (NCS) at a single, large tertiary referral center. PATIENTS AND METHODS: Electronic medical records from September 2, 2005, through May 31, 2012, were retrospectively reviewed to evaluate the perioperative management and outcomes in LVAD patients undergoing NCS. Patients were included only if they required a general anesthetic and had previously been discharged from the hospital after initial LVAD implantation. RESULTS: Thirty-three patients with LVADs underwent general anesthesia for 67 noncardiac operations. The mean ± SD time from LVAD implantation to NCS was 317 ± 349 days. All but 1 patient had axial flow LVADs. Anticoagulation or antiplatelet agents were present within 7 days before NCS in 49 procedures (73%) and reversed in 32 of 49 (65%). No perioperative thrombotic complications related to anticoagulation or antiplatelet reversal were noted. Red blood cell, fresh frozen plasma, and platelet transfusions were administered during 10, 6, and 4 operations, respectively. The only intraoperative complication was surgical bleeding. Postoperative complications were present in 12 patients after NCS and were mainly composed of bleeding. Three patients died within 30 days of NCS, with the causes of death not attributed to NCS. CONCLUSION: Patients with LVAD safely underwent NCS in a multidisciplinary setting that included preoperative optimization by cardiologists familiar with LVADs when feasible. Anticoagulation or antiplatelet agents were present preoperatively in most patients with LVADs and were safely reversed when necessary for NCS. The relatively high occurrence of postoperative bleeding is consistent with previous series.

Dual anti-platelet therapy after coronary artery bypass grafting: is there any benefit? A systematic review and meta-analysis.

BACKGROUND: Anti-platelet therapy is an important component of medical therapy post coronary artery bypass grafting (CABG). While aspirin administration is a Class I indication after CABG, the benefit of concomitant clopidogrel is a controversial issue. METHODS: We searched OVID Medline, Cochrane, Scopus, and EMBASE for randomized control trials and observational studies comparing aspirin ± placebo to aspirin + clopidogrel after CABG. RESULTS: Eleven articles (five randomized control trials and six observational studies) including 25,728 patients met inclusion criteria. Early saphenous vein graft occlusion was reduced with the use of dual anti-platelet therapy (risk ratio (RR) = 0.59, 95% CI 0.43-0.82, p = 0.02). In-hospital or 30-day mortality was lower with aspirin + clopidogrel (0.8%) compared to aspirin alone (1.9%) (p < 0.0001), while risk of angina or perioperative myocardial infarction was comparable (RR = 0.60, 95% CI 0.31-1.14, p = 0.12). Patients treated with aspirin + clopidogrel demonstrated a trend towards a higher incidence of major bleeding episodes as compared to patients treated with aspirin alone (RR = 1.17, 95% CI 1.00-1.37, p = 0.05). In a pooled analysis of studies involving off-pump CABG compared to aspirin alone, dual anti-platelet therapy reduced the risk of perioperative myocardial infarction and saphenous graft occlusion by 68% (47% to 71%) and 55% (2% to 79%) respectively. CONCLUSION: Dual anti-platelet therapy after CABG improved early saphenous vein graft patency, but may increase the risk of bleeding. The use of dual anti-platelet therapy appears to be most beneficial in patients undergoing off-pump CABG. Prospective randomized studies are necessary to determine whether this beneficial effect of dual therapy is also achieved in patients undergoing on pump CABG.

Bilateral internal thoracic artery harvest and deep sternal wound infection in diabetic patients.

BACKGROUND: Coronary artery bypass graft surgery is superior to percutaneous intervention in diabetic patients with multivessel disease. The use of bilateral internal thoracic arteries (BITA) may provide better long-term graft patency, but the risk of postoperative deep sternal wound infection has limited its use in diabetic patients. However, studies have reported conflicting results, and require systematic evaluation. METHODS: MEDLINE, EMBASE, World of Science, and the Cochrane library were searched for randomized controlled trials and observational studies comparing the incidence of deep sternal wound infection in diabetic patients undergoing either left internal thoracic artery (LITA) or BITA harvest. We used random effect models to compare risk ratios within groups. RESULTS: One randomized controlled trial and 10 observational studies (126,235 diabetic patients: 122,465 LITA, 3,770 BITA) met inclusion criteria. Deep sternal wound infection occurred in 3.1% and 1.6% for the BITA and LITA cohorts, respectively. The risk ratio for deep sternal wound infection development was 1.71 (1.37 to 2.14) for BITA compared with LITA. Patients who underwent skeletonized BITA harvest had a similar risk of deep sternal wound infection compared with LITA (0.9 [0.42 to 2.09]), although pedicled harvest demonstrated increased risk (1.77 [1.4 to 2.23]). Early mortality was comparable in the LITA cohort (2.5%) and the BITA cohort (2.3%; p = 0.8). CONCLUSIONS: The risk of deep sternal wound infection can be minimized in diabetic patients undergoing coronary artery bypass graft surgery by performing ITA harvested in a skeletonized manner with meticulous attention to preserving sternal blood flow. Pedicled harvest is to be discouraged when utilizing both ITA owing to a significant increase in the risk of postoperative deep sternal wound infection.

Predictive value of the model for end-stage liver disease score in patients undergoing left ventricular assist device implantation.

Axial flow left ventricular assist device (LVAD) implantation is an effective therapy for patients with advanced heart failure. As the preoperative hepatic and renal function play a critical role in determining adverse events after LVAD implantation, we analyzed the predictive role of the model for end-stage liver disease (MELD) score in determining in-hospital mortality after surgery. One hundred twenty-six patients underwent implant of an LVAD at our institution. Their individual preoperative MELD scores and perioperative total blood product usage (TBPU) were calculated. As LVAD implant as a reoperation is known to influence postoperative bleeding and mortality independently, the patients were divided into group I (first cardiac surgery) and group II (reoperative surgery). Group I: LVAD implantation was performed in 68/126 (54%) patients as their first cardiac surgery. The mean MELD score was 16.3 ± 6. Median TBPU for this group was 20.7 (0, 135) units. Inhospital mortality/30-day mortality was 4/68 (5.8%). Increasing MELD score (c-statistic = 0.88) and TBPU were found to be predictors of early mortality. An increasing MELD score was associated with more TBPU (p < 0.01) with a 10.9 ± 3 TBPU increase per a 10 unit rise in the MELD score. Group II: Of the 126 patients, 58 (46%) underwent LVAD implantation as a reoperation. Mean MELD score for these patients was 16 ± 5. Inhospital mortality/30-day mortality in this group was 12% and median TBPU was 30 (4,153) units. The MELD score was not predictive of inhospital mortality in these patients (p = 0.97). The MELD score is predictive of early mortality in patients undergoing LVAD implantation as their first cardiac surgery. Use of this score to select patients for LVAD implantation may be appropriate.

Ventricular fibrillation in an ambulatory patient supported by a left ventricular assist device: highlighting the ICD controversy.

Left ventricular assist devices (LVADs) provide an effective means of managing advanced pump failure as a means of bridging to cardiac transplantation or as permanent therapy. Although ventricular arrhythmias remain common post-LVAD implantation, such therapy may allow malignant arrhythmias to be tolerated hemodynamically. This report describes the clinical findings in a patient who had likely been in a ventricular tachyarrhythmia for several days and presented in ventricular fibrillation, ambulatory, and mentating normally. This report, with previous similar reports, is additive to the body of evidence that LVADs alter the physiologic impact of ventricular arrhythmias in advanced heart failure and highlights the need for thoughtful programming of implantable cardioverter defibrillator therapies in these patients.

Echocardiographic variables after left ventricular assist device implantation associated with adverse outcome.

BACKGROUND: Operative mortality after left ventricular assist device (LVAD) implantation is heavily influenced by patient selection and the technical difficulty of surgery. However, how we treat our patients and LVAD setting may affect the patient outcome beyond this period. We postulated that the presence of echocardiographic variables 1 month after surgery suggesting appropriate degree of LV unloading and an adequate forward flow would be important in determining clinical outcomes after the initial successful LVAD implantation. METHODS AND RESULTS: We retrospectively analyzed various variables in echocardiographic examinations performed 30 days after LVAD implant in 76 consecutive patients receiving continuous flow device for their association with a compound end point (90-day mortality, readmission for heart failure, or New York Heart Association class III or higher at the end of the 90-day period). The echocardiographic associations examined included estimated LVAD flow, with and without native LV contribution, interventricular septal position, the status of aortic valve opening, an estimated left atrial pressure (ELAP), the mitral flow E-wave deceleration time, and the ratio of deceleration time to E-wave velocity (mitral deceleration index [MDI]). Four patients died during the 30- to 90-day period, 6 patients were readmitted for heart failure, and 25 patients were considered to have New York Heart Association class III or higher at the end of the 90-day period. Variables associated with adverse outcome included increased ELAP (odds ratio, 1.30 [1.16-1.48]; P<0.0001), MDI <2 ms/[cm/s] (odds ratio, 4.4 implantation [1.22-18]; P=0.02) and decreased tricuspid lateral annulus velocity (odds ratio, 0.70 implantation [0.48-0.95]; P=0.02). A leftward deviation of interventricular septum was associated with a worse outcome (odds ratio, 3.03 implantation [1.21-13.3]; P=0.01). CONCLUSIONS: Mortality and heart failure after LVAD surgery appear to be predominantly determined by echocardiographic evidence of inefficient unloading of the left ventricle and persistence of right ventricular dysfunction. Increased estimated LA pressure and short MDI are associated with worse mid term outcome. Leftward deviation of the septum is associated with worse outcome as well.

Palliative medicine consultation for preparedness planning in patients receiving left ventricular assist devices as destination therapy.

OBJECTIVE: To assess the benefit of proactive palliative medicine consultation for delineation of goals of care and quality-of-life preferences before implantation of left ventricular assist devices as destination therapy (DT). PATIENTS AND METHODS: We retrospectively reviewed the cases of patients who received DT between January 15, 2009, and January 1, 2010. RESULTS: Of 19 patients identified, 13 (68%) received proactive palliative medicine consultation. Median time of palliative medicine consultation was 1 day before DT implantation (range, 5 days before to 16 days after). Thirteen patients (68%) completed advance directives. The DT implantation team and families reported that preimplantation discussions and goals of care planning made postoperative care more clear and that adverse events were handled more effectively. Currently, palliative medicine involvement in patients receiving DT is viewed as routine by cardiac care specialists. CONCLUSION: Proactive palliative medicine consultation for patients being considered for or being treated with DT improves advance care planning and thus contributes to better overall care of these patients. Our experience highlights focused advance care planning, thorough exploration of goals of care, and expert symptom management and end-of-life care when appropriate.

Echocardiographic predictors of adverse outcomes after continuous left ventricular assist device implantation.

OBJECTIVES: The purpose of the study was to identify echocardiographic predictors of adverse outcome in patients implanted with continuous-flow left ventricular assist devices (LVAD). BACKGROUND: Continuous flow LVAD have become part of the standard of care for the treatment of advanced heart failure. However, knowledge of echocardiographic predictors of outcome after LVAD are lacking. METHODS: Overall, 83 patients received continuous-flow LVAD (HeartMate II, Thoratec Corporation, Pleasanton, California) from February 2007 to June 2010. The LVAD database, containing various echocardiographic parameters, was examined to analyze their influence on in-hospital mortality, a compound cardiac event (in-hospital mortality or acute right ventricular [RV] dysfunction), and long-term mortality. RESULTS: Eight patients died before discharge (operative mortality 9.6%), and another 15 patients were considered to have acute RV dysfunction immediately after surgery. Patients with relatively small left ventricular end-diastolic diameters (<63 mm) had significantly higher risk for in-hospital mortality (odds ratio [OR]: 0.9; 95% confidence interval [CI]: 0.83 to 0.99; p = 0.04) or occurrence of the compound cardiac event (OR: 0.89; 95% CI: 0.84 to 0.95; p < 0.001). The most significant predictor of outcome was the decreased timing interval between the onset and the cessation of tricuspid regurgitation flow corrected for heart rate (TRDc), a surrogate for early systolic equalization of RV and right atrial pressure. Short TRDc predicted in-hospital mortality (OR: 0.85; 95% CI: 0.74 to 0.97; p = 0.01) and the compound cardiac event (OR: 0.83; 95% CI: 0.74 to 0.91; p < 0.0001). Multivariate analysis based on a logistic regression model demonstrated that the accuracy of predicting the 30-day compound adverse outcome was improved with the addition of echocardiographic variables when added to the commonly used hemodynamic or clinical scores. TRDc predicted long-term survival, with adjusted risk ratios of 0.89 for death from any cause (95% CI: 0.83 to 0.96; p = 0.003) and 0.88 for cardiac-related death (95% CI: 0.77 to 0.98; p = 0.03). CONCLUSIONS: The presence of either a relatively small left ventricle (<63 mm) or early systolic equalization of RV and right atrial pressure (short TRDc) demonstrated by echocardiography is associated with increased 30-day morbidity and mortality. Prediction of early adverse outcomes by echocardiographic parameters is additive to laboratory or hemodynamic variables.

Regulation of circulating progenitor cells in left ventricular dysfunction.

BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

Nonrevascularizable coronary artery disease following coronary artery bypass graft surgery: a population-based study in Olmsted County, Minnesota.

AIMS: Therapeutic options for patients with recurrent cardiac ischemia after coronary artery bypass surgery may be limited and some patients may be considered nonrevascularizable. To further the understanding of this patient cohort, we performed a population-based study of post-coronary bypass patients who developed recurrent angina. METHODS AND RESULTS: Patients who underwent coronary artery and bypass graft angiography at Mayo Clinic from 2001 to 2005 were identified. Medical records were reviewed to determine indication for angiography, and angiographic analysis was performed in all patients. Among 133 000 residents of Olmsted County, Minnesota, 347 post-bypass patients with angina underwent coronary angiography from 2001 to 2005. Of these, 177 patients received further revascularization (145 percutaneous coronary intervention and 32 redo coronary artery bypass grafting) and the remaining 170 patients were managed medically. Revascularization was not associated with improvement in all-cause or cardiac mortality. Multivariate analysis identified renal dysfunction, diabetes, and severe left ventricular dysfunction but not the lack of revascularization as predictors of mortality. CONCLUSION: In this population-based study, we identified a yearly incidence range of 17.9-33.2 patients with nonrevascularizable angina after coronary artery bypass grafting per 100 000 population. Further revascularization was not associated with improved mortality or morbidity. Attempts to develop therapeutics for this population must consider the incidence and outcomes of this cohort.

Late allograft failure after heart transplantation: 2 unusual cases.

Cardiac allograft failure is most commonly caused by acute rejection and cardiac allograft vasculopathy. Consequently, heart transplant recipients who present with heart failure are empirically treated at many transplant centers with augmented immunosuppression despite negative endomyocardial biopsies. We report 2 unusual cases of acute allograft dysfunction that highlight the importance of caution in adopting an empiric strategy of profound immunosuppression in the absence of objective data to support graft rejection.

Circulating CD34+ cell subsets in patients with coronary endothelial dysfunction.

BACKGROUND: Endothelial dysfunction is an early manifestation of atherosclerotic disease. Circulating cells that express CD34, including endothelial and hematopoietic progenitor cells, might play a part in the development and progression of atherosclerosis. The aim of this study was to evaluate the association between coronary endothelial dysfunction and concentrations of circulating CD34+ cell subsets. METHODS: Intracoronary acetylcholine challenge was used to test for coronary endothelial dysfunction in 57 consecutive patients scheduled to undergo diagnostic coronary angiography and with no signs of substantial obstructive lesions. Mononuclear cells were extracted from whole blood samples taken from all patients, analyzed by flow cytometry for CD14, CD34, CD133, CD45, and vascular endothelial growth factor receptor 2 (VEGFR2), and cultured for functional analysis. RESULTS: Compared with patients with normal coronary endothelial function, in those with coronary endothelial dysfunction, the number of circulating CD34+/CD45(dim)/VEGFR2- cells, CD34+/CD45(dim)/CD133+/VEGFR2- cells and colony-forming units were reduced. Concentrations of CD34+/CD45-/VEGFR2+ cells did not differ between groups. CONCLUSIONS: Regulation of CD34+ cell subsets seems to differ between patients with coronary endothelial dysfunction and those with normal coronary endothelial function. Changes in specific circulating progenitor cell subsets might, therefore, be an early manifestation of atherosclerosis.